Biology subjects

Rosin, N.

Publications and source records attributed to Rosin, N..

5 recordsLinked to original sources

bioRxiv2024

The Diversified Astrocyte Developmental Programs are Modulated by Primary Ciliary Signaling

Astrocyte diversity is greatly influenced by local environmental modulation. Here, we report that the vast majority of brain astrocytes across the entire brain possess a singular primary cilium, a specialized signaling antenna localized to cell soma. Comparative single-cell transcriptomics reveals that primary cilia mediate canonical Shh signaling to modulate astrocyte subtype-specific core features in synaptic regulation, intracellular transport, energy and metabolism. Independent of canonical Shh signaling, primary cilia are important regulators for astrocyte morphology and intracellular signaling balance. Dendritic spine analysis and transcriptomics reveal that perturbation of astrocytic cilia leads to disruption of neuronal development and global intercellular connectomes in the brain. Ultimately, mice with primary ciliary deficient astrocytes show behavioral deficits in sensorimotor function, sociability, learning and memory. Our results uncover a critical role for primary cilia in transmitting local cues that drive the region-specific diversification of astrocytes within the developing brain.

neuroscience↗

bioRxiv2024

A single-cell transcriptomics atlas for the parasitic nematode Heligmosomoides bakeri: Extrapolating model organism information to non-model systems

Single-cell atlases aim to collect the gene expression information for every cell type in an organism but can be challenging to perform in non-model organisms. To try to circumvent the problem of having no verified cell type markers in the parasitic nematode Heligmosomoides bakeri to use for an atlas, we attempted to use orthologs of verified markers from the closely related model organism Caenorhabditis elegans. This resulted in a useful comparison between the two worms for each of the cell types recovered in preliminary H. bakeri single-cell RNA-sequencing. For H. bakeri males and females, robustly recovered cell types include the gametes, embryos, and male intestine, while hypodermis, neurons, muscles, and pharyngeal cells were under-represented cell types. The two worms appear to have a similar hypodermis, cuticle, eggshell, and spermatogenesis process. On the other hand, putative cell identities and cell cycle scores suggest the intestine and muscle cells in H. bakeri may still be cycling and dividing, unlike in C. elegans. Additionally, embryogenesis and early development appear to be quite different between the two worms, with only eight out of 94 confirmed paternal contributions to the embryo in C. elegans (with an ortholog) predicted to also be paternal contributions in H. bakeri. Overall, this new dataset allowed me to move beyond the presence or absence of orthologs to include their tissue specificity and expression level similarities and differences when comparing these two worms to better identify biological processes and traits in a parasitic nematode that are modelled well by C. elegans.

developmental biology↗

bioRxiv2023

A genetic program for vascular pericyte precursors

Brain pericytes are one of the critical cell types that regulate endothelial barrier function and activity, thus ensuring adequate blood flow to the brain. The genetic pathways guiding undifferentiated cells into mature pericytes are not well understood. We show here that pericyte precursor populations from both neural crest and head mesoderm of zebrafish express the transcription factor nkx3.1 develop into brain pericytes. We identify the gene signature of these precursors, and show that an nkx3.1, foxf2a, and cxcl12b -expressing pericyte precursor population is present around the basilar artery prior to artery formation and pericyte recruitment. The precursors later spread throughout the brain and differentiate to express canonical pericyte markers. Cxcl12b-Cxcr4 signaling is required for pericyte attachment and differentiation. Further, both nkx3.1 and cxcl12b are necessary and sufficient in regulating pericyte number as loss inhibits and gain increases pericyte number. Through genetic experiments we have defined a precursor population for brain pericytes and identified genes critical for their differentiation.

developmental biology↗

bioRxiv2022

A Protocol for Single Nucleus RNAseq from Frozen Skeletal Muscle

Single cell technologies are a method of choice to obtain vast amounts of cell-specific transcriptional information under physiological and diseased states. Myogenic cells are resistant to single nucleus RNA sequencing (snRNAseq) due to their large, multinucleated nature. Here, we report a novel, reliable, and cost-effective method to analyze frozen human skeletal muscle by snRNAseq. This method yields all expected cell types for human skeletal muscle and works on tissue frozen for long periods of time and with significant pathological changes. Our method is ideal for studying banked samples with the intention of studying human muscle disease.

genomics↗

bioRxiv2021

An Immune Cell Atlas Reveals Dynamic COVID-19 Specific Neutrophil Programming Amendable to Dexamethasone Therapy

SARS-CoV-2 is a novel coronavirus that causes acute respiratory distress syndrome (ARDS), death and long-term sequelae. Innate immune cells are critical for host defense but are also the primary drivers of ARDS. The relationships between innate cellular responses in ARDS resulting from COVID-19 compared to other causes of ARDS, such as bacterial sepsis is unclear. Moreover, the beneficial effects of dexamethasone therapy during severe COVID-19 remain speculative, but understanding the mechanistic effects could improve evidence-based therapeutic interventions. To interrogate these relationships, we developed an scRNA-Seq and plasma proteomics atlas (biernaskielab.ca/COVID_neutrophil). We discovered that compared to bacterial ARDS, COVID-19 was associated with distinct neutrophil polarization characterized by either interferon (IFN) or prostaglandin (PG) active states. Neutrophils from bacterial ARDS had higher expression of antibacterial molecules such as PLAC8 and CD83. Dexamethasone therapy in COVID patients rapidly altered the IFNactive state, downregulated interferon responsive genes, and activated IL1R2+ve neutrophils. Dexamethasone also induced the emergence of immature neutrophils expressing immunosuppressive molecules ARG1 and ANXA1, which were not present in healthy controls. Moreover, dexamethasone remodeled global cellular interactions by changing neutrophils from information receivers into information providers. Importantly, male patients had higher proportions of IFNactive neutrophils, a greater degree of steroid-induced immature neutrophil expansion, and increased mortality benefit compared to females in the dexamethasone era. Indeed, the highest proportion of IFNactive neutrophils was associated with mortality. These results define neutrophil states unique to COVID-19 when contextualized to other life-threatening infections, thereby enhancing the relevance of our findings at the bedside. Furthermore, the molecular benefits of dexamethasone therapy are also defined, and the identified pathways and plasma proteins can now be targeted to develop improved therapeutics.

immunology↗